In the fetus, net oxidation of the hydroxy group of corticosteroids at C-11, which is dominant early in development, later gives way to reduction of the 11-dehydro-corti-costeroids. This shift is essential to survival in the perinatal period. From evidence in the literature, we suggest that there are distinct oxidases and reductases that catalyze the transformations at C-11, and that these are under separate genetic control. 11-oxidases and 11 reductases will be isolated from adult rat liver, fetal rat tissues, and from fibroblasts and epithelial cells of fetal rat lung grown in tissue culture. They will be characterized by kinbetic and physicochemical methods. Their identity will be tested by immunizing rabbits with the purest preparations and determining cross reactivity of the various enzymes with the resulting natibody. The effect of age, strain, sex treatment of rats with hormones (triodothyronine, steroids) on oxidative and reductive enzyme activity will be evaluated. We will be able to (a) determine how oxidation and reduction at C-11 are independently affected by environmental and developmental factors: (b) provide the basic data that would justify further genetic studeis on the expression of 11 -hydroxy-steroid dehydrogenase; (c) provide a rational explanation for an provide a mechanism to explain disturbances in 11 -hydroxysteroid dehydrogenase in man.